The thyroid gland, among other things, modulates a body's energy metabolism. It does so by releasing various iodinated thyronines. Two of these iodinated thyronines are thyroxine (3,5,3',5'-tetraiodothyronine or "T-4") and liothyronine (3,5,3'-triiodothyronine or "T-3").
Various diseases affecting the thyroid or pituitary gland can result in hypothyroidism. Hypothyroidism can also result from thyroid surgery or treatment with radioactive iodine. In a "hypothyroid" state, the body's basal metabolic state drops, and growth and development may be impaired.
Hypothyroidism is usually treated by administering exogenous "thyroid hormone" (actually a combination of thyroxine and liothyronine) or levothyroxine or liothyronine alone.
Other treatments include administering combination dosage forms containing a 4:1 mixture of levothyroxine to liothyronine. Such combination dosage forms are commonly called "liotrix tablets" and are available under the trademark names "Euthroid" (Parke-Davis) and "Thyrolar" (Rorer). Such tablets typically contain 25 .mu.g:6.25 .mu.g, 30 .mu.g:7.5 .mu.g, 50 .mu.g:12.5 .mu.g, 60 .mu.g:15 .mu.g, 100 .mu.g:25 .mu.g, 150 .mu.g:37.5 .mu.g, or 180 .mu.g:45 .mu.g (levothyroxine: liothyronine).
This 4 to 1 ratio of T-4 to T-3 is carried forward pretty much consistently in the patent literature. For example, U.S. Pat. Nos. 3,577,535 and 3,477,954 broadly disclose ratios varying from 2.3:1 (EXAMPLE I) to 8:1 (EXAMPLE III), but 4:1 is still seen as ideal. WO 91/06569 discloses a iodothyronine polymer which may have sustained release properties, but the 4 to 1 ratio is still preferred even though the disclosed ratios do vary from 70 to 90% T-4 with 10 to 30% T-3.
Treatment of hypothyroidism even with these combination preparations can still result in undesirable side effects, such as angina, palpitations, an increased incidence of osteoporosis, and hypertension.
Furthermore, with tablets containing only T-4, if a higher than normal thyroxine to liothyronine plasma level results, subnormal TSH levels appear, apparently due to the pituitary being in a state of thyrotoxicosis. This thyrotoxicosis may also affect other organs and systems of the body.